Noninvasive stratification of postinfarction rats based on the degree of cardiac dysfunction using magnetic resonance imaging and echocardiography

Abstract

The myocardial infarction (MI) rat model plays a crucial role in modern cardiovascular research, but the inherent heterogeneity of this model represents a challenge. We sought to identify subgroups among the post-MI rats and establish simple noninvasive stratification protocols for such subgroups. Six weeks after induction of MI, 49 rats underwent noninvasive examinations using magnetic resonance imaging (MRI) and echocardiography. Twelve sham-operated rats served as controls. Increased end-diastolic left ventricular (LV) pressure and lung weight served as indicators for congestive heart failure (CHF). A clustering algorithm using 13 noninvasive and invasive parameters was used to identify distinct groups among the animals. The cluster analysis revealed four distinct post-MI phenotypes; two without congestion but with different degree of LV dilatation, and two with different degree of congestion and right ventricular (RV) affection. Among the MRI parameters, RV mass emerged as robust noninvasive marker of CHF with 100% specificity/sensitivity. Moreover, LV infarct size and RV ejection fraction further predicted subgroup among the non-CHF and CHF rats with excellent specificity/sensitivity. Of the echocardiography parameters, left atrial diameter predicted CHF. Moreover, LV end-diastolic diameter predicted the subgroups among the non-CHF rats. We propose two simple noninvasive schemes to stratify post-MI rats, based on the degree of heart failure; one for MRI and one for echocardiography. In vivo phenotyping of rats is essential for robust and reliable data. Here, we present two simple noninvasive schemes for the stratification of postinfarction rats based on the degree of heart failure: one using magnetic resonance imaging and one based on echocardiography.

Guidelines for experimental models of myocardial ischemia and infarction

“…Cardiac wound healing and remodeling, typically assessed days to weeks post-MI, can be examined using a wide variety of approaches, including echocardiography, histology, biochemistry, and cell biology ( 5 , 217 , 328 ). Serial measurements of cardiac geometry and function by echocardiography are useful for defining phenotypes.…”

Cardiomyocyte substructure reverts to an immature phenotype during heart failure

“…Myocardial infarction was induced in male Wistar rats (ß300 g, 10 weeks old) as described previously (Aronsen et al 2017). In short, rats were intubated and kept under anaesthesia with a mixture of 65% N 2 O, 32% O 2 , and 2-3% isoflurane.…”

Echocardiographic Assessment of Cardiac Anatomy and Function in Adult Rats

“…It is important to note that there are some advantages in using murine or rodent models. The short gestation period, low cost of breeding and housing, the knowledge of their genome and possibility to develop transgenic animals are the main advantages of these species, making them attractive to study the mechanisms involved in cardiovascular disease 4,5,6,7,8,9 .…”

“…Although rat and mouse models show similar advantages, rats are the classical choice in cardiovascular studies due to their larger physical dimension and lower heart rate that provides better images in echocardiography studies 4,5,6,7,8,9,10 .…”

“…The electrocardiographic monitorization integrated in the equipment is very prone to artifacts, which is a constraint. Also, it is very important to state that the functional or hemodynamic cardiac status of the rat can depend on variables such as temperature, blood pressure and heart rate 4,5,6,7,8,9,13,14,17 .…”